Catalysis in Water: Aldol‐Type Reaction of Aldehydes and Imines with Ethyl Diazoacetate Catalyzed by Highly Basic Magnesium/Lanthanum Mixed Oxide

Abstract

Magnesium/lanthanum mixed oxide is an effective heterogeneous catalyst for aldol-type condensation of aldehydes and imines with ethyl diazoacetate (EDA) at room temperature in water to afford corresponding b-hydroxy-a-diazo carbonyl compounds and b-amino-a-diazo carbonyl compounds in good yields. The catalyst is recovered and reused for several cycles with consistent activity.Keywords: b-amino-a-diazo carbonyl compounds; b-hydroxy-a-diazo carbonyl compounds; heterogeneous catalyst; magnesium/lanthanum mixed oxide; water as solvent a-Diazo carbonyl compounds [1] are a potential source of amino alcohols and acids. a-Diazo carbonyl compounds are generally prepared by the azido transfer reaction of carbonyl compounds.[2] Condensation of acyldiazomethane to aldehydes and imines also yields a-diazo carbonyl compounds but requires deprotonation of the acyldiazomethane. This is usually carried out by using strong bases, such as butyllithium, [3] lithium diisopropylamide (LDA), [4] sodium hydride, [5] potassium hydroxide, [6] [7] and quarternary ammonium hydroxide.[8] However, some of the methods require low temperatures and absolutely anhydrous conditions, moreover the use of such strong bases may not be compatible with functional groups in the substrates. Thus, the development of more improved synthetic methods for the preparation of a-diazo carbonyl compounds remains an active research area.In recent years, there has been increasing emphasis on the use and design of environment-friendly solid catalysts to reduce the amount of toxic waste. The use of a solid catalyst allows easy separation of catalyst from the reaction mixture in large-scale production to conform to the concept of green technology. In a recent review, Sheldon [9] emphasized the point that "the best solvent is no solvent and if a solvent (diluent) is needed then water is preferred. Water is nontoxic, non-flammable, abundantly available and inexpensive" therefore, reactions performed in water are safer and cheaper.We herein report the synthesis of b-hydroxy-adiazo carbonyl compounds and b-amino-a-diazo carbonyl compounds by condensation of a wide variety of aldehydes and imines with ethyl diazoacetate using the Mg/La mixed oxide catalyst in water (Scheme 1).To the best of our knowledge, there are no reports on this condensation using a heterogeneous catalyst and water as solvent. The Mg/La mixed oxide catalyst was prepared by the co-precipitation method described earlier.[10] Chemical analysis of the solid gave the composition La 2 O 3 29.5 %, MgO: 30.1 %, K 2 O: 3.4 %, H 2 O: 37 %. The catalyst is well characterized by XRD, DTA coupled with mass spectrometry, FTIR and calorimetry. This mixed oxide is macroporous and shows a surface area of 37.6 m 2 g À1 after calcination at 923 K. Recently, we have efficiently performed transesterifications of diethyl carbonate by alcohols [11] and Michael addition reactions [10] by using this highly Scheme 1.

Benzoic Acid Catalyzed Aldol‐Type Condensation of Aldehydes with Ethyl Diazoacetate: Highly Diastereoselective Products with Chiral Aldehydes

“…The conventional method of nucleophilic addition of an acyldiazomethane to an aldehyde or ketone requires deprotonation of acyldiazomethane to generate highly reactive anionic species. Such an essential deprotonation is usually achieved by treatment of the acyldiazomethane with strong bases such as butyllithium,5 lithium diisopropylamide (LDA),6 sodium hydride (NaH),7 potassium hydroxide (KOH),8 1,8‐diazabicyclo[5,4,0]undec‐7‐ene (DBU),9 quaternary ammonium hydroxide,10 or Mg/La mixed oxide 11. Although the anionic species thus generated can efficiently add to carbonyl compounds, some of these methods clearly require strongly basic reagents and cryogenic, anhydrous conditions.…”

A Green Protocol for the Synthesis of α‐Diazo‐β‐hydroxyesters and One‐Pot Conversion to β‐Keto‐Esters and Imidazo[1,2‐a]pyridine‐3‐carboxylates

“…As expected, these structurally diverse aliphatic aldehydes also underwent the reaction and furnished the respective α‐diazo‐β‐hydroxy esters ( 3 w‐3 y ) in moderate to good yields (Scheme ). The synthesized products 3 a‐l , 3 o‐p , 3 s‐y are already known in the literature whereas the unknown compounds 3 m & 3 r have been characterized by different spectral analysis.…”

“…Moreover, strong bases are incompatible with the substrates bearing base sensitive functional groups. Again, solid base catalysts such as nanocrystalline MgO, MgO/La 2 O 3 , silica supported tetramethylguanidine and KF/nano‐clinoptilolite are showing good to excellent catalytic activity in promoting this important transformation. Although, these heterogeneous bases have very good potential in terms of conversion and yield of the reaction, their tedious process of preparation may rule them out from practical application in large scale.…”

Copper‐Impregnated Magnesium‐Lanthanum Mixed Oxide: A Reusable Heterogeneous Catalyst for Allylation of Aldehydes and Ketones

“…Figueras and co‐workers examined the direct condensation of alcohols and Michael addition reactions over highly basic Mg−La mixed oxide catalyst. The catalytic activity of the Mg−La mixed oxide was demonstrated in the condensation of aldehydes and imines with ethyl diazoacetate using water as a solvent . Various transition‐metals impregnated Mg−La mixed oxide catalysts have also been developed and used as effective heterogeneous catalysts in various organic transformations .…”